CA1051905A - Acide 1,3-dioxo-2-isoindolinacetique, 1 n-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamidomethylene/hydrazides - Google Patents

Acide 1,3-dioxo-2-isoindolinacetique, 1 n-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamidomethylene/hydrazides

Info

Publication number: CA1051905A
Authority: CA; Canada
Prior art keywords: chloro; dioxo; methyl; triazol; benzophenone
Prior art date: 1974-06-19
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA310,228A

Other languages

English (en)

Inventor

Martin Gall

Jackson B. Hester (Jr.)

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Pharmacia and Upjohn Co

Original Assignee

Upjohn Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1974-06-19

Filing date

1978-08-29

Publication date

1979-04-03

1974-06-19 Priority claimed from US05/480,979 external-priority patent/US3957761A/en

1975-05-22 Priority claimed from CA227,597A external-priority patent/CA1055490A/fr

1978-08-29 Application filed by Upjohn Co filed Critical Upjohn Co

1979-04-03 Application granted granted Critical

1979-04-03 Publication of CA1051905A publication Critical patent/CA1051905A/fr

Status Expired legal-status Critical Current

Links

125000000325 methylidene group Chemical group [H]C([H])=* 0.000 title claims description 24
PAUAJOABXCGLCN-UHFFFAOYSA-N n-(1,3-dioxo-2-benzofuran-4-yl)acetamide Chemical compound CC(=O)NC1=CC=CC2=C1C(=O)OC2=O PAUAJOABXCGLCN-UHFFFAOYSA-N 0.000 title claims description 22
229940042795 hydrazides for tuberculosis treatment Drugs 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 19
150000001875 compounds Chemical class 0.000 claims abstract description 18
239000001257 hydrogen Substances 0.000 claims abstract description 11
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
238000004519 manufacturing process Methods 0.000 claims abstract description 4
229910052736 halogen Chemical group 0.000 claims abstract 3
150000002367 halogens Chemical group 0.000 claims abstract 3
239000003960 organic solvent Substances 0.000 claims abstract 2
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 4
239000007858 starting material Substances 0.000 claims description 4
239000000126 substance Substances 0.000 claims 3
BXBSDHSVTCGOFC-UHFFFAOYSA-N 3-amino-4-phenylquinazolin-4-ol Chemical compound NN1C=NC2=CC=CC=C2C1(O)C1=CC=CC=C1 BXBSDHSVTCGOFC-UHFFFAOYSA-N 0.000 claims 1
ZAXFFQSOWYVGER-UHFFFAOYSA-N 3-amino-6-chloro-4-phenylquinazolin-4-ol Chemical compound NN1C=NC2=CC=C(Cl)C=C2C1(O)C1=CC=CC=C1 ZAXFFQSOWYVGER-UHFFFAOYSA-N 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
-1 pyrrolidino, piperidino Chemical group 0.000 abstract description 16
125000001153 fluoro group Chemical group F* 0.000 abstract description 7
239000000543 intermediate Substances 0.000 abstract description 6
125000001309 chloro group Chemical group Cl* 0.000 abstract description 5
125000000217 alkyl group Chemical group 0.000 abstract description 4
125000004432 carbon atom Chemical group C* 0.000 abstract description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 3
125000001246 bromo group Chemical group Br* 0.000 abstract description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 2
208000019901 Anxiety disease Diseases 0.000 abstract 1
241000124008 Mammalia Species 0.000 abstract 1
230000036506 anxiety Effects 0.000 abstract 1
125000001424 substituent group Chemical group 0.000 abstract 1
239000012965 benzophenone Substances 0.000 description 84
229940024874 benzophenone Drugs 0.000 description 81
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 76
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 32
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 29
239000000725 suspension Substances 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
239000012346 acetyl chloride Substances 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 14
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 13
229940049706 benzodiazepine Drugs 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 11
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 11
239000000047 product Substances 0.000 description 11
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
239000000203 mixture Substances 0.000 description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
239000000243 solution Substances 0.000 description 6
150000002431 hydrogen Chemical class 0.000 description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
239000012267 brine Substances 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000000538 analytical sample Substances 0.000 description 3
150000008366 benzophenones Chemical class 0.000 description 3
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 3
125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 3
QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 3
VGIVLIHKENZQHQ-UHFFFAOYSA-N n,n,n',n'-tetramethylmethanediamine Chemical compound CN(C)CN(C)C VGIVLIHKENZQHQ-UHFFFAOYSA-N 0.000 description 3
FEQAUBVIUZJXKN-UHFFFAOYSA-N propan-2-imine;hydrochloride Chemical compound [Cl-].CC(C)=[NH2+] FEQAUBVIUZJXKN-UHFFFAOYSA-N 0.000 description 3
239000007787 solid Substances 0.000 description 3
MXVWWBLMLHYVOZ-UHFFFAOYSA-N 1-[8-chloro-6-(2,6-difluorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylmethanamine Chemical compound C12=CC(Cl)=CC=C2N2C(CN(C)C)=NN=C2CN=C1C1=C(F)C=CC=C1F MXVWWBLMLHYVOZ-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
239000005977 Ethylene Substances 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
125000005587 carbonate group Chemical group 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
NUSHELRLSJLWBO-UHFFFAOYSA-N n-[(8-chloro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methyl]-n-ethylethanamine Chemical compound C12=CC(Cl)=CC=C2N2C(CN(CC)CC)=NN=C2CN=C1C1=CC=CC=C1 NUSHELRLSJLWBO-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
QHYNXXQYSDCYJU-UHFFFAOYSA-N (6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methanamine Chemical class C12=CC=CC=C2N2C(CN)=NN=C2CN=C1C1=CC=CC=C1 QHYNXXQYSDCYJU-UHFFFAOYSA-N 0.000 description 1
125000001401 1,2,4-triazol-4-yl group Chemical group N=1N=C([H])N([*])C=1[H] 0.000 description 1
DWCNNQOORRREID-UHFFFAOYSA-N 1,2-dichloroethane;methanol Chemical compound OC.ClCCCl DWCNNQOORRREID-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
KQISQNCCCASSDX-UHFFFAOYSA-N 1-(pyrrolidin-1-ylmethyl)pyrrolidine Chemical compound C1CCCN1CN1CCCC1 KQISQNCCCASSDX-UHFFFAOYSA-N 0.000 description 1
RXCBJYLIJODACT-UHFFFAOYSA-N 1-[6-(2-chlorophenyl)-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylmethanamine Chemical compound C12=CC(C(F)(F)F)=CC=C2N2C(CN(C)C)=NN=C2CN=C1C1=CC=CC=C1Cl RXCBJYLIJODACT-UHFFFAOYSA-N 0.000 description 1
NFKBEJFYDAYBSB-UHFFFAOYSA-N 1-[6-(2-chlorophenyl)-8-fluoro-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylmethanamine Chemical compound C12=CC(F)=CC=C2N2C(CN(C)C)=NN=C2CN=C1C1=CC=CC=C1Cl NFKBEJFYDAYBSB-UHFFFAOYSA-N 0.000 description 1
DIPFASDTUQPOIP-UHFFFAOYSA-N 1-[6-(2-chlorophenyl)-8-nitro-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylmethanamine Chemical compound C12=CC([N+]([O-])=O)=CC=C2N2C(CN(C)C)=NN=C2CN=C1C1=CC=CC=C1Cl DIPFASDTUQPOIP-UHFFFAOYSA-N 0.000 description 1
RTRYDCCPKISLAY-UHFFFAOYSA-N 1-[9-bromo-6-(2,6-difluorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]-n,n-dimethylmethanamine Chemical compound C12=CC=C(Br)C=C2N2C(CN(C)C)=NN=C2CN=C1C1=C(F)C=CC=C1F RTRYDCCPKISLAY-UHFFFAOYSA-N 0.000 description 1
ZMBGDHSFLFMTPQ-UHFFFAOYSA-N 1-methyl-4-[(4-methylpiperazin-1-yl)methyl]piperazine Chemical compound C1CN(C)CCN1CN1CCN(C)CC1 ZMBGDHSFLFMTPQ-UHFFFAOYSA-N 0.000 description 1
FGMJNFYMDMPABN-UHFFFAOYSA-M 1-methylidenepyrrolidin-1-ium;chloride Chemical compound [Cl-].C=[N+]1CCCC1 FGMJNFYMDMPABN-UHFFFAOYSA-M 0.000 description 1
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
SOFQRBRMIYVJRT-UHFFFAOYSA-N 2,4-dimethylpentan-3-ylideneazanium;chloride Chemical compound [Cl-].CC(C)C(=[NH2+])C(C)C SOFQRBRMIYVJRT-UHFFFAOYSA-N 0.000 description 1
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
VWVRASTUFJRTHW-UHFFFAOYSA-N 2-[3-(azetidin-3-yloxy)-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound O=C(CN1C=C(C(OC2CNC2)=N1)C1=CN=C(NC2CC3=C(C2)C=CC=C3)N=C1)N1CCC2=C(C1)N=NN2 VWVRASTUFJRTHW-UHFFFAOYSA-N 0.000 description 1
LPZOCVVDSHQFST-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CC LPZOCVVDSHQFST-UHFFFAOYSA-N 0.000 description 1
JVKRKMWZYMKVTQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JVKRKMWZYMKVTQ-UHFFFAOYSA-N 0.000 description 1
UEKRWFIZYRRPGN-UHFFFAOYSA-N 2-[[4-(2-benzoyl-3-nitrophenyl)-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound [O-][N+](=O)C1=CC=CC(N2C(=NN=C2)CN2C(C3=CC=CC=C3C2=O)=O)=C1C(=O)C1=CC=CC=C1 UEKRWFIZYRRPGN-UHFFFAOYSA-N 0.000 description 1
NMLSQGQMTQVIDO-UHFFFAOYSA-N 2-[[4-(2-benzoyl-4-bromophenyl)-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound C=1C(Br)=CC=C(N2C(=NN=C2)CN2C(C3=CC=CC=C3C2=O)=O)C=1C(=O)C1=CC=CC=C1 NMLSQGQMTQVIDO-UHFFFAOYSA-N 0.000 description 1
PEKIJLFAGGYWKY-UHFFFAOYSA-N 2-[[4-(2-benzoyl-4-chlorophenyl)-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound C=1C(Cl)=CC=C(N2C(=NN=C2)CN2C(C3=CC=CC=C3C2=O)=O)C=1C(=O)C1=CC=CC=C1 PEKIJLFAGGYWKY-UHFFFAOYSA-N 0.000 description 1
BPVLNMCPQSPBAM-UHFFFAOYSA-N 2-[[4-(2-benzoyl-4-nitrophenyl)-5-[(dimethylamino)methyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound CN(C)CC1=NN=C(CN2C(C3=CC=CC=C3C2=O)=O)N1C1=CC=C([N+]([O-])=O)C=C1C(=O)C1=CC=CC=C1 BPVLNMCPQSPBAM-UHFFFAOYSA-N 0.000 description 1
IFGZUICJFWRSDO-UHFFFAOYSA-N 2-[[4-(2-benzoylphenyl)-5-[(dimethylamino)methyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound CN(C)CC1=NN=C(CN2C(C3=CC=CC=C3C2=O)=O)N1C1=CC=CC=C1C(=O)C1=CC=CC=C1 IFGZUICJFWRSDO-UHFFFAOYSA-N 0.000 description 1
BVENAPNHXSNXPZ-UHFFFAOYSA-N 2-[[4-[2-(2-chlorobenzoyl)-4-(trifluoromethyl)phenyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound C=1C(C(F)(F)F)=CC=C(N2C(=NN=C2)CN2C(C3=CC=CC=C3C2=O)=O)C=1C(=O)C1=CC=CC=C1Cl BVENAPNHXSNXPZ-UHFFFAOYSA-N 0.000 description 1
PBVJCTNMQNFWLT-UHFFFAOYSA-N 2-[[4-[2-(2-chlorobenzoyl)-4-fluorophenyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound C=1C(F)=CC=C(N2C(=NN=C2)CN2C(C3=CC=CC=C3C2=O)=O)C=1C(=O)C1=CC=CC=C1Cl PBVJCTNMQNFWLT-UHFFFAOYSA-N 0.000 description 1
JWBVUHHLOMZGOY-UHFFFAOYSA-N 2-[[4-[2-(2-chlorobenzoyl)-4-fluorophenyl]-5-[(dimethylamino)methyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound CN(C)CC1=NN=C(CN2C(C3=CC=CC=C3C2=O)=O)N1C1=CC=C(F)C=C1C(=O)C1=CC=CC=C1Cl JWBVUHHLOMZGOY-UHFFFAOYSA-N 0.000 description 1
JEIOTAMEWZRGEH-UHFFFAOYSA-N 2-[[4-[2-(3-bromobenzoyl)-4-chlorophenyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound C=1C(Cl)=CC=C(N2C(=NN=C2)CN2C(C3=CC=CC=C3C2=O)=O)C=1C(=O)C1=CC=CC(Br)=C1 JEIOTAMEWZRGEH-UHFFFAOYSA-N 0.000 description 1
JNAKGWMCGUIQCA-UHFFFAOYSA-N 2-[[4-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-[[di(propan-2-yl)amino]methyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound CC(C)N(C(C)C)CC1=NN=C(CN2C(C3=CC=CC=C3C2=O)=O)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl JNAKGWMCGUIQCA-UHFFFAOYSA-N 0.000 description 1
LXKHUPSNFJCLOL-UHFFFAOYSA-N 2-[[4-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-[[ethyl(methyl)amino]methyl]-1,2,4-triazol-3-yl]methyl]isoindole-1,3-dione Chemical compound CCN(C)CC1=NN=C(CN2C(C3=CC=CC=C3C2=O)=O)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl LXKHUPSNFJCLOL-UHFFFAOYSA-N 0.000 description 1
WMIDNZIENCUDQB-UHFFFAOYSA-N 3-amino-4-(2-chlorophenyl)-6-(trifluoromethyl)quinazolin-4-ol Chemical compound NN1C=NC2=CC=C(C(F)(F)F)C=C2C1(O)C1=CC=CC=C1Cl WMIDNZIENCUDQB-UHFFFAOYSA-N 0.000 description 1
ODDVBNFQXOOFHM-UHFFFAOYSA-N 3-amino-4-(2-chlorophenyl)-6-fluoroquinazolin-4-ol Chemical compound NN1C=NC2=CC=C(F)C=C2C1(O)C1=CC=CC=C1Cl ODDVBNFQXOOFHM-UHFFFAOYSA-N 0.000 description 1
CZMHBYPVOXHRAL-UHFFFAOYSA-N 6-(2-chlorophenyl)-1-(piperidin-1-ylmethyl)-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine Chemical compound C=1C(C(F)(F)F)=CC=C(N23)C=1C(C=1C(=CC=CC=1)Cl)=NCC3=NN=C2CN1CCCCC1 CZMHBYPVOXHRAL-UHFFFAOYSA-N 0.000 description 1
241000271566 Aves Species 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241000243251 Hydra Species 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
241001024304 Mino Species 0.000 description 1
FPQQZBFOOHVTQY-UHFFFAOYSA-N N-[[4-chloro-2-(2-chlorobenzoyl)-N-[2-(1,3-dioxoisoindol-2-yl)acetyl]anilino]methylideneamino]-2-(1,3-dioxoisoindol-2-yl)acetamide Chemical compound C=1C(Cl)=CC=C(N(C=NNC(=O)CN2C(C3=CC=CC=C3C2=O)=O)C(=O)CN2C(C3=CC=CC=C3C2=O)=O)C=1C(=O)C1=CC=CC=C1Cl FPQQZBFOOHVTQY-UHFFFAOYSA-N 0.000 description 1
PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
XBIPSSUMUYALFF-UHFFFAOYSA-M [Cl-].C(CC)C=[N+]=CCCC Chemical compound [Cl-].C(CC)C=[N+]=CCCC XBIPSSUMUYALFF-UHFFFAOYSA-M 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
230000000049 anti-anxiety effect Effects 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000002301 combined effect Effects 0.000 description 1
KSWZQIKAXKUXJM-UHFFFAOYSA-M di(propylidene)azanium;chloride Chemical compound [Cl-].CCC=[N+]=CCC KSWZQIKAXKUXJM-UHFFFAOYSA-M 0.000 description 1
WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
JROFLKHMJKJKJA-UHFFFAOYSA-M ethyl-methyl-methylideneazanium;chloride Chemical compound [Cl-].CC[N+](C)=C JROFLKHMJKJKJA-UHFFFAOYSA-M 0.000 description 1
238000000605 extraction Methods 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
239000005457 ice water Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
UNEXJVCWJSHFNN-UHFFFAOYSA-N n,n,n',n'-tetraethylmethanediamine Chemical compound CCN(CC)CN(CC)CC UNEXJVCWJSHFNN-UHFFFAOYSA-N 0.000 description 1
LQXZYQVIANZLKS-UHFFFAOYSA-N n,n-dimethyl-1-(8-nitro-6-phenyl-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)methanamine Chemical compound C12=CC([N+]([O-])=O)=CC=C2N2C(CN(C)C)=NN=C2CN=C1C1=CC=CC=C1 LQXZYQVIANZLKS-UHFFFAOYSA-N 0.000 description 1
RQHUKNYXQSLRQB-UHFFFAOYSA-N n,n-dimethyl-1-[6-phenyl-8-(trifluoromethyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]methanamine Chemical compound C12=CC(C(F)(F)F)=CC=C2N2C(CN(C)C)=NN=C2CN=C1C1=CC=CC=C1 RQHUKNYXQSLRQB-UHFFFAOYSA-N 0.000 description 1
HPVUTFZVVTXQGB-UHFFFAOYSA-N n-[[6-(2-chlorophenyl)-8-nitro-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]methyl]-n-methylethanamine Chemical compound C12=CC([N+]([O-])=O)=CC=C2N2C(CN(C)CC)=NN=C2CN=C1C1=CC=CC=C1Cl HPVUTFZVVTXQGB-UHFFFAOYSA-N 0.000 description 1
QJJXKGKSFWBILZ-UHFFFAOYSA-N n-[[8-chloro-6-(2-chlorophenyl)-4h-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl]methyl]-n-propan-2-ylpropan-2-amine Chemical compound C12=CC(Cl)=CC=C2N2C(CN(C(C)C)C(C)C)=NN=C2CN=C1C1=CC=CC=C1Cl QJJXKGKSFWBILZ-UHFFFAOYSA-N 0.000 description 1
KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000002936 tranquilizing effect Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Landscapes

Indole Compounds (AREA)

CA310,228A 1974-06-19 1978-08-29 Acide 1,3-dioxo-2-isoindolinacetique, 1 n-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamidomethylene/hydrazides Expired CA1051905A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US05/480,979 US3957761A (en)	1973-02-14	1974-06-19	Process for the production of 1-aminomethyl-6-phenyl-4h-s-triazolo-[4,3-a][1]benzodiazepines and intermediates
CA227,597A CA1055490A (fr)	1974-06-19	1975-05-22	Procede pour la preparation de triazolobenzodiazepines

Publications (1)

Publication Number	Publication Date
CA1051905A true CA1051905A (fr)	1979-04-03

Family

ID=25667957

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA310,228A Expired CA1051905A (fr)	1974-06-19	1978-08-29	Acide 1,3-dioxo-2-isoindolinacetique, 1 n-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamidomethylene/hydrazides

Country Status (1)

Country	Link
CA (1)	CA1051905A (fr)

1978
- 1978-08-29 CA CA310,228A patent/CA1051905A/fr not_active Expired

Publication	Publication Date	Title
SU786899A3 (ru)	1980-12-07	Способ получени производных 1-(1,3-диоксолан-2-илметил)-1н-имидазолов или-1н-1,2, 4-триазолов или их кислотно-аддитивных солей, в виде смеси или отдельных стереоизомеров
US4788210A (en)	1988-11-29	1,2,4-Triazole compounds
CN1926114B (zh)	2011-08-24	用于制备经取代n-芳基-n′-′3-(1h-吡唑-5-基)苯基脲及其中间体的方法
US4495185A (en)	1985-01-22	1,2,4-Triazin-3(2H) ones
EP0285893B1 (fr)	1992-03-18	Dérivé de phényltriazole et insecticide
US4517197A (en)	1985-05-14	-N-substituted phenyl-5-methoxymethyl-2-oxazolidinones and pharmaceutical compositions containing same
Bonacorso et al.	2006	Trifluoromethyl-containing pyrazolinyl (p-tolyl) sulfones: The synthesis and structure of promising antimicrobial agents
RU2243220C2 (ru)	2004-12-27	Имидазольные соединения, способ их получения, способ ингибирования аденозиндезаминазы и фармацевтическая композиция на их основе
US4489074A (en)	1984-12-18	1,3,4-Thiadiazin-2-ones
JP3781464B2 (ja)	2006-05-31	オキサゾール中間体を介するアリールピロール殺虫剤の製造法
FR2649612A1 (fr)	1991-01-18	Medicaments a base de derives de 1h-benzoxadiazine-4,1,2 nouveaux derives et leurs procedes de preparation
GB2454290A (en)	2009-05-06	1,2,4-triazoles useful as 5-hydroxytryptamine agonists
CZ357392A3 (en)	1993-08-11	Process for preparing mono-n-substituted tetraazamacrocycles
CA1051905A (fr)	1979-04-03	Acide 1,3-dioxo-2-isoindolinacetique, 1 n-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamidomethylene/hydrazides
JPS61152661A (ja)	1986-07-11	１，２，４‐トリアゾール誘導体
CA1055490A (fr)	1979-05-29	Procede pour la preparation de triazolobenzodiazepines
US4871757A (en)	1989-10-03	Heterocyclic compounds
JPH08283261A (ja)	1996-10-29	３−フェニルトリアゾール誘導体および殺虫、殺ダニ剤
US4001222A (en)	1977-01-04	3-(Aminoacyl)-1-{[5-(substituted phenyl)furfurylidene]amino}hydantoins and process for their preparation thereof
JP3496078B2 (ja)	2004-02-09	新規なヒドラゾン誘導体及びその製造法
Horvath et al.	2013	Synthesis of some 1, 4-disubstituted thiosemicarbazides as intermediates for the synthesis of 1, 3, 4-thiadiazole derivatives
Komaraiah et al.	2007	Bisheterocycles: Synthesis of some novel 1, 2, 3-triazolyl oxadiazole and 4 (3H)-quinazolinones via azide cycloaddition reaction
US3957761A (en)	1976-05-18	Process for the production of 1-aminomethyl-6-phenyl-4h-s-triazolo-[4,3-a][1]benzodiazepines and intermediates
Sarkate et al.	2019	Copper-catalyzed Convenient Synthesis and SAR Studies of Substituted-1, 2, 3-triazole as Antimicrobial Agents
EP0590834A1 (fr)	1994-04-06	Dérives de phénylimidazole, procédés pour leur production, herbicides contenant les dits dérivés et l'utilisation des dits herbicides